Burn-induced reductions in mitochondrial abundance and efficiency are more pronounced with small volumes of colloids in swine

Tony Chao, Belinda I. Gómez, Tiffany C. Heard, Brian W. Smith, Michael A. Dubick, David M. Burmeister

Research output: Contribution to journalArticle

Abstract

Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria are currently unknown. The purpose of this study is to determine cardiac mitochondrial function in a swine burn model with subsequent resuscitation using either crystalloids or colloids. Anesthetized Yorkshire swine (n = 23) sustained 40% total body surface area burns and received IV crystalloids (n = 11) or colloids (n = 12) after recovery from anesthesia. Non-burned swine served as controls (n = 9). After euthanasia at 48 h, heart tissues were harvested, permeabilized, and analyzed by high-resolution respirometry. Citrate synthase (CS) activity was measured, and Western blots were performed to quantify proteins associated with mitochondrial fusion (OPA1), fission (FIS1), and mitophagy (PINK1). There were no differences in state 2 respiration or maximal oxidative phosphorylation. Coupled complex 1 respiration decreased, while uncoupled state 4O and complex II increased significantly due to burn injury, particularly in animals receiving colloids (P < 0.05). CS activity and electron transfer coupling efficiency were significantly lower in burned animals, particularly with colloid treatment (P < 0.05). Protein analysis revealed increased FIS1 but no differences in mitophagy in cardiac tissue from colloid-treated compared with crystalloid-treated swine. Taken together, severe burns alter mitochondrial respiration in heart tissue, which may be exacerbated by early IV resuscitation with colloids. Early IV burn resuscitation with colloids may require close hemodynamic observation. Mitochondrial stabilizing agents incorporated into resuscitation fluids may help the hemodynamic response to burn injury.

Original languageEnglish (US)
Pages (from-to)C1229-C1238
JournalAmerican Journal of Physiology - Cell Physiology
Volume317
Issue number6
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Colloids
Burns
Swine
Resuscitation
Mitochondrial Degradation
Citrate (si)-Synthase
Respiration
Hemodynamics
Wounds and Injuries
Mitochondrial Dynamics
Euthanasia
Excipients
Body Surface Area
Oxidative Phosphorylation
Critical Care
Cardiac Myocytes
Mitochondria
Proteins
Homeostasis
Anesthesia

Keywords

  • Burn
  • Heart
  • Mitochondria
  • Resuscitation
  • Swine

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Burn-induced reductions in mitochondrial abundance and efficiency are more pronounced with small volumes of colloids in swine. / Chao, Tony; Gómez, Belinda I.; Heard, Tiffany C.; Smith, Brian W.; Dubick, Michael A.; Burmeister, David M.

In: American Journal of Physiology - Cell Physiology, Vol. 317, No. 6, 01.01.2019, p. C1229-C1238.

Research output: Contribution to journalArticle

Chao, Tony ; Gómez, Belinda I. ; Heard, Tiffany C. ; Smith, Brian W. ; Dubick, Michael A. ; Burmeister, David M. / Burn-induced reductions in mitochondrial abundance and efficiency are more pronounced with small volumes of colloids in swine. In: American Journal of Physiology - Cell Physiology. 2019 ; Vol. 317, No. 6. pp. C1229-C1238.
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AB - Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria are currently unknown. The purpose of this study is to determine cardiac mitochondrial function in a swine burn model with subsequent resuscitation using either crystalloids or colloids. Anesthetized Yorkshire swine (n = 23) sustained 40% total body surface area burns and received IV crystalloids (n = 11) or colloids (n = 12) after recovery from anesthesia. Non-burned swine served as controls (n = 9). After euthanasia at 48 h, heart tissues were harvested, permeabilized, and analyzed by high-resolution respirometry. Citrate synthase (CS) activity was measured, and Western blots were performed to quantify proteins associated with mitochondrial fusion (OPA1), fission (FIS1), and mitophagy (PINK1). There were no differences in state 2 respiration or maximal oxidative phosphorylation. Coupled complex 1 respiration decreased, while uncoupled state 4O and complex II increased significantly due to burn injury, particularly in animals receiving colloids (P < 0.05). CS activity and electron transfer coupling efficiency were significantly lower in burned animals, particularly with colloid treatment (P < 0.05). Protein analysis revealed increased FIS1 but no differences in mitophagy in cardiac tissue from colloid-treated compared with crystalloid-treated swine. Taken together, severe burns alter mitochondrial respiration in heart tissue, which may be exacerbated by early IV resuscitation with colloids. Early IV burn resuscitation with colloids may require close hemodynamic observation. Mitochondrial stabilizing agents incorporated into resuscitation fluids may help the hemodynamic response to burn injury.

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